EU/3/10/775

Orphan designation

For a list of the administrative updates to this public summary of opinion, please refer to the PDF document below.

On 20 September 2010, orphan designation (EU/3/10/775) was granted by the European Commission to t2cure GmbH, Germany, for autologous bone-marrow-derived mononuclear-cell fraction for the treatment of thromboangiitis obliterans (Buerger's disease).

Thromboangiitis obliterans, also known as Buerger’s disease, is a disease in which the blood vessels become inflamed. Because of the inflammation, clots form within the blood vessels, blocking them and causing pain. The small blood vessels in the limbs (especially in the hands, legs and feet) are most often affected, and the lack of blood flow can cause skin ulcers (sores) and gangrene (decay and death of tissue). Ultimately, the limb may need to be amputated. Although the causes of the inflammation in thromboangiitis obliterans are not known, the disease is known to be closely linked to smoking.

Thromboangiitis obliterans is a long-term debilitating condition because of the development of ulcers and gangrene, and the risk of amputation.

At the time of designation, thromboangiitis obliterans affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of designation, iloprost was authorised in some EU Member States for the treatment of advanced thromboangiitis obliterans. Other medicines were also used to control the symptoms of the disease such as pain, and to promote the healing of the skin ulcers. Vascular surgery (surgery on the blood vessels) was used in a small number of cases.

The sponsor has provided sufficient information to show that autologous bone-marrow-derived mononuclear-cell fraction might be of significant benefit for patients with thromboangiitis obliterans because it works in a different way to existing treatments and might act on the original underlying lesions causing the disease. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Autologous bone-marrow-derived mononuclear-cell fraction is an advanced medicine that belongs to the group called ‘somatic-cell-therapy products’. These are medicines that contain cells or tissues that have been manipulated to change their biological characteristics so that they can be used to cure, diagnose or prevent a disease.

Autologous bone-marrow-derived mononuclear-cell fraction is made of stem cells extracted from the patient’s own bone marrow. Stem cells are cells that can develop into different types of cell. This medicine is expected to be injected directly into the patient’s affected blood vessels, where the stem cells are expected to move towards the damaged areas and promote the growth of new blood vessels. This will improve the blood supply in these areas, relieving the symptoms of the disease.

The effects of autologous bone-marrow-derived mononuclear-cell fraction have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with autologous bone-marrow-derived mononuclear-cell fraction in patients with thromboangiitis obliterans were ongoing.

At the time of submission, autologous bone-marrow-derived mononuclear-cell fraction was not authorised anywhere in the EU for thromboangiitis obliterans. Orphan designation had been granted in the United States for thromboangiitis obliterans.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 2010 recommending the granting of this designation.

the existence of alternative methods of diagnosis, prevention or treatment;

either the rarity of the condition (affecting not more than 5 in 10,000 people in the European Union) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.